The overall objective of this research project has been the delineation of some of the genetic factors that regulate specific immune responses. The research has focused on two animal models, each representing a different facet of the immune response that is under the direct control of a single genetic locus. We have been studying histocompatibility-linked immune response genes in guinea pigs as a model of genetic control at the level of antigen recognition, the afferent arm of the immune response. In addition, we have recently uncovered a gene regulating the magnitude of the antibody-forming cell response of mouse lymphocytes to the hapten TNP in tissue culture. TNP specific B cell precursors from animals lacking the gene appear to be defective in their ability to be stimulated to antibody-forming cells. This experimental model then provides the opportunity to examine the genetic regulation of antibody production and efferent arm of the immune response. Current studies on these model systems are directed at (1) defining the role of I region histocompatibility antigens in antigen recognition and (2) determining the nature of the B cell defect in mice genetically unable to make a substantial anti-TNP antibody forming cell response in culture.